Study protocol: computerised cognitive testing in a cohort of people with frontotemporal dementia

Introduction The term frontotemporal dementia (FTD) refers to a heterogeneous group of neurodegenerative disorders affecting the frontal and temporal lobes. Cognitively, impairment of executive function and social cognition predominates across the FTD spectrum, although other domains can be affected. Traditionally, cognition is tested through standard ‘pen and paper’ tasks in FTD. However, recent attempts have been made across other neurodegenerative disorders such as Alzheimer’s disease to develop computerised batteries that allow more accurate and sensitive detection of cognitive impairment. Methods and analysis This paper describes the development of a novel battery of tests for a tablet computer, particularly focused on FTD. It consists of 12 different tasks which aim to tap into information processing speed, various aspects of executive function, social cognition, semantic knowledge, calculation and visuospatial skills. Future studies will focus on validating the battery in a healthy control cohort, comparing it against a standard ‘pen and paper’ psychometric battery, and finally testing it within an FTD cohort, including those with genetic forms of FTD where we will be able to assess its ability to detect very early cognitive deficits prior to the onset of symptoms. Ethics and dissemination Normative data will be produced in the initial validation study (approved by the UCL Ethics Committee, project ID 17691/002) and will be made available online.

This is an elegant protocol addressing a relevant question: whether FTD assessment can be done in computerized, short, selfadminister, and portable (home) settings. A strength of the protocol is the very well-detailed tasks and the chance to validate this protocol in a large cohort with pre-clinical presentations. Overall, I think this is an excellent proposal that could interest many readers of the BMJ Open. However, I think the authors should address a few minor points detailed below.
1) Although there are no current computer versions specifically devoted to FTD, there are multiple batteries (i.e., Examiner, miniSEA) and table assessment tools such as TabCAT. The authors may clarify the advantages of Ignite concerning these other available protocols.
2) How will Caregivers interact with the Tablet? And how patient data won't be contaminated by caregiver interventions? What are the planned quality checks for individual assessment at home? This may be a bit challenging considering the case of patients with dementia.
3) The authors state that the complete set of tasks requires around 30 minutes or less. I wonder if this has already been tested in patients? (especially in self-assessment settings?) 4. Some parts of the protocol may be very challenging for some FTD patients, such as the 2-back task. How will the authors assess engagement, missing data and assure tasks completion? 5) I would like to learn about how the protocol is designed regarding software platform, feedback and instruction for users, encryption system and data safety, ethical regulation and confidentiality, interoperability, access to internet and data sharing process, data repository, and potential interface for results and outcomes. Can the authors comment on these issues?

VERSION 1 -AUTHOR RESPONSE
Reviewer: 1 Some comments and recommendations to the protocol: 1. Measure the disparity between letter and semantic fluency performance could help differentiate FTD from other dementias (AD). Does Ignite evaluate fluency? If not, why?
We do not evaluate fluency. We would need to do this either by getting people to speak into the app for verbal fluency (which we do not have capacity to do) or write in the app for written fluency -we have avoided any tests that include writing a specific word in the app as this is extremely difficult to programme and score, particularly in different languages. All tests are just a simple single tap.

What are the inclusion and exclusion criteria for the participants?
3. How many participants? 4. How will the sample size be calculated?
The paper describes the development of the app and not future specific studies of this. As discussed the initial study will be of a healthy control cohort in comparison to a standard psychometric battery.
5. The specific aims are not well established.
The aim was to develop an app which could be used in frontotemporal dementia, particularly for trials. This is outlined in the final paragraph of the introduction. The specific objectives in developing the battery are outlined in the section called 'Objectives for developing a computerized cognitive battery' in the Methods.
6. The statistical analysis that will be used should be described in the methodology for each objective.
As above, the paper is setting out the development of the app and not future specific studies of this. Each study will require a specific statistical analysis.

Reviewer: 2
This is an elegant protocol addressing a relevant question: whether FTD assessment can be done in computerized, short, self-administer, and portable (home) settings. A strength of the protocol is the very well-detailed tasks and the chance to validate this protocol in a large cohort with pre-clinical presentations. Overall, I think this is an excellent proposal that could interest many readers of the BMJ Open. However, I think the authors should address a few minor points detailed below. 1) Although there are no current computer versions specifically devoted to FTD, there are multiple batteries (i.e., Examiner, miniSEA) and table assessment tools such as TabCAT. The authors may clarify the advantages of Ignite concerning these other available protocols.
Thank you for the comment -at present, the clear advantage is the computerised nature (and therefore ability to do remotely). However, as other tablet assessments like the TabCAT become more widely available such as through the ALLFTD study it will be very helpful to compare Ignite with those -we have added a section on future comparisons with tests developed through other studies such as ALLFTD in the discussion.
2) How will Caregivers interact with the Tablet? And how patient data won't be contaminated by caregiver interventions? What are the planned quality checks for individual assessment at home? This may be a bit challenging considering the case of patients with dementia.
As outlined in the Introduction, the app is designed to be used in people who are presymptomatic or in the very early symptomatic stages of FTD. We would not expect this to be used (and therapeutic trials are not being performed) in people with moderate to severe dementia i.e. at the stage of requiring a caregiver. We have clarified this in the paper.
3) The authors state that the complete set of tasks requires around 30 minutes or less. I wonder if this has already been tested in patients? (especially in self-assessment settings?) We have piloted this in people with presymptomatic and early symptomatic FTD and this is the time it takes.
4. Some parts of the protocol may be very challenging for some FTD patients, such as the 2-back task. How will the authors assess engagement, missing data and assure tasks completion?
As per above, the app is designed to be used in people who are presymptomatic or in the very early symptomatic stages of FTD-we would not expect this to be used in people with moderate to severe dementia. Pilot studies show that this is feasible in this population. As per above, we have clarified this in the paper. 5) I would like to learn about how the protocol is designed regarding software platform, feedback and instruction for users, encryption system and data safety, ethical regulation and confidentiality, interoperability, access to internet and data sharing process, data repository, and potential interface for results and outcomes. Can the authors comment on these issues?
Thank you -the initial version of the app has been designed to be used on an iPad only and available via the App Store (although future versions hopefully will include other tablets). The data is currently stored on the iPad and then removed from that once the iPad is returned and stored on the local server. No additional interface has currently been designed. We have clarified some of these issues now in the paper. However, many we have not yet needed to address with the current versionnonetheless, we agree that all these issues mentioned are important with future iterations of the app aiming to solve some of them.